A Toll-like receptor recognizes bacterial DNA

@article{Hemmi2000ATR,
  title={A Toll-like receptor recognizes bacterial DNA},
  author={Hiroaki Hemmi and Osamu Takeuchi and Taro Kawai and Tsuneyasu Kaisho and Shintaro Sato and Hideki Sanjo and Makoto Matsumoto and Katsuaki Hoshino and Hermann Wagner and Kiyoshi Takeda and Shizuo Akira},
  journal={Nature},
  year={2000},
  volume={408},
  pages={740-745}
}
DNA from bacteria has stimulatory effects on mammalian immune cells, which depend on the presence of unmethylated CpG dinucleotides in the bacterial DNA. In contrast, mammalian DNA has a low frequency of CpG dinucleotides, and these are mostly methylated; therefore, mammalian DNA does not have immuno-stimulatory activity. CpG DNA induces a strong T-helper-1-like inflammatory response. Accumulating evidence has revealed the therapeutic potential of CpG DNA as adjuvants for vaccination strategies… Expand
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  • Biology, Medicine
  • Annual review of immunology
  • 2002
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The data indicate that bacterial DNA preparations from different species differ in their capacity to activate TLR-9, which is dependent on the individual [CG] content, and increased intracellular delivery results in a marked enhancement of immunostimulation. Expand
Differences in Macrophage Activation by Bacterial DNA and CpG-Containing Oligonucleotides1
TLDR
The structural differences between E. coli DNA and PO-ODN are assessed, which may explain the high activity of bacterial DNA on macrophages and the length dependence of the CpG ODN response was found to correlate with the presence in macrophage of a length-dependent uptake process for DNA. Expand
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Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition
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It is shown that human TLR9 expression in human immune cells correlates with responsiveness to bacterial deoxycytidylate-phosphate-deoxyguanylate (CpG)-DNA, and data suggest that hTLR9 conveys CpG-DNA responsiveness to human cells by directly engaging immunostimulating Cpg-DNA. Expand
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References

SHOWING 1-10 OF 31 REFERENCES
CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells.
TLDR
The ability of specific CpG motifs to strongly activate certain subsets of human DCs to promote Th1-like immune responses is demonstrated, and the use of C pG DNA-based trials for immunotherapy against cancer, allergy, and infectious diseases is supported. Expand
CpG motifs in bacterial DNA trigger direct B-cell activation
TLDR
The potent immune activation by CpG oligon nucleotides has impli-cations for the design and interpretation of studies using 'antisense' oligonucleotides and points to possible new applications as adjuvants. Expand
Bacterial CpG DNA activates immune cells to signal infectious danger.
  • H. Wagner
  • Biology, Medicine
  • Advances in immunology
  • 1999
TLDR
Compelling evidence now shows that the prokaryotic DNA—through pattern recognition—is sensed by cells of the immune system, thereby signaling “infectious danger,” and there is a change in the view of interplay between the innate and the adaptive immune system. Expand
Rapid induction of mitogen-activated protein kinases by immune stimulatory CpG DNA.
TLDR
The results indicate that CpG DNA activates the p38 and c-Jun NH2-terminal kinase MAPK and leads to the activation of AP-1 via a pathway which is sensitive to chloroquine. Expand
The discovery of immunostimulatory DNA sequence.
TLDR
DNA purified from BCG inhibited the growth of various animal tumors, augmented cell activity and induced IFN from mouse spleen cells, and DNA from bacteria, but not animals and plants, showed the above-mentioned immunogical activity. Expand
Activation of cutaneous dendritic cells by CpG-containing oligodeoxynucleotides: a role for dendritic cells in the augmentation of Th1 responses by immunostimulatory DNA.
TLDR
It is concluded that immunostimulatory CpG ODN stimulate DC in vitro and in vivo and that bacterial DNA-based vaccines may preferentially elicit Th1-predominant immune responses because they activate and mobilize DC and induce them to produce large amounts of IL-12. Expand
Immune Cell Activation by Bacterial Cpg-DNA through Myeloid Differentiation Marker 88 and Tumor Necrosis Factor Receptor–Associated Factor (Traf)6
TLDR
The data suggest that CpG-DNA initiates signaling via the TLR/IL-1R pathway in APCs in a manner similar to LPS and to T helper cell–mediated CD40 ligation. Expand
Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells
TLDR
It is demonstrated that bacterial DNA or i.s. CpG‐ODN cause maturation and activation of DC to bring about conversion of immature DC into professional APC, which is associated with the acquisition of professional antigen‐presenting cell (APC) function. Expand
CpG-DNA-Mediated Transient Lymphadenopathy Is Associated with a State of Th1 Predisposition to Antigen-Driven Responses1
TLDR
CpG-DNA instigated a local predisposition for intense CTL responses and Th1-polarized immune responses to subsequent infections or Ag challenge, which could represent a capacitating immune reaction yielding rapid conditioned responses to secondary infections. Expand
Macrophages sense pathogens via DNA motifs: induction of tumor necrosis factor‐α‐mediated shock
TLDR
DNA of gram‐positive and gram‐negative bacteria or certain synthetic oligonucleotides displaying unmethylated CpG‐motifs can trigger macrophages in vitro to induce nuclear translocation of nuclear factor‐xB, accumulate tumor necrosis factor (TNF)‐α mRNA and release large amounts of TNF‐α. Expand
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...